tbuckley/cabot-search huggingface dataset:
Dissolving microneedles: Applications and growing therapeutic potential
Authors: Ziad Sartawi, Caroline Blackshields, Waleed Faisal
Journal: Journal of Controlled Release (2022)

Microneedles are a rapidly developing method for the transdermal delivery of therapeutic compounds. All types of microneedles, whether solid, hollow, coated, or dissolving function by penetrating the stratum corneum layer of the skin producing a microchannel through which therapeutic agents may be delivered. To date, coated and hollow microneedles have been the most successful, despite suffering from issues such as poor drug loading capabilities and blocked pores. Dissolving microneedles, on the other hand, have superior drug loading as well as other positive attributes that make it an ideal delivery system, including simple methods of fabrication and disposal, and abundantly available materials. Indeed, dissolvable microneedles can even be fabricated entirely from the therapeutic agent itself thus eliminating the requirement for additional excipients. This focused review presents the recent developments and trends of dissolving microneedles as well as potential future directions. The advantages, and disadvantages of dissolving microneedles as well as fabrication materials and methods are discussed. The potential applications of dissolving microneedles as a drug delivery system in different therapeutic areas in both research literature and clinical trials is highlighted. Applications including the delivery of cosmetics, vaccine delivery, diagnosis and monitoring, cancer, pain and inflammation, diabetes, hair and scalp disorders and inflammatory skin diseases are presented. The current trends observed in the microneedle landscape with particular emphasis on contemporary clinical trials and commercial successes as well as barriers impeding microneedle development and commercialisation are also discussed.
Spatial transcriptomic profiling of prostate cancer reveals zone specific androgen receptor signaling and immune infiltration
Authors: P. Patel, S. Nallandhighal, D. Scoville, L. Tran, B. Cotta, A. Udager, A. Rao, G. Palapattu, V. Dadhania, S. Pitchiaya, S. Salami
Journal: European Urology (2022)
The impact of anthracycline-based chemotherapy on fatigue: Results from WF-97415.
Authors: Nancy E Avis, Beverly J Levine, Shannon L. Mihalko, Heidi D. Klepin, Peter H. Brubaker, Tonya Calhoun, Susan Faye Dent, Mary Helen Hackney, Bonnie Ky, Amy Ladd, William Ofori Ntim, Lynne I. Wagner, Kathryn E. Weaver, W. Gregory Hundley
Journal: Journal of Clinical Oncology (2022)

e24115 Background: Chemotherapy (CT) is one of the most common factors associated with fatigue among breast cancer (BC) patients. However, there is a paucity of research on the impact of different types of CT on fatigue, specifically, whether women who receive anthracycline-based (Anth) CT experience greater fatigue than those who receive non-anthracycline-based (noAnth) CT. Methods: Analyses are from the longitudinal Understanding and Predicting fatigue, cardiovascular decline, and events after BrEast cAncer sTudy (UPBEAT: WF 97415)), conducted through the NCI Community Oncology Research Program (NCORP). We compared fatigue 3-months after initiating cancer treatment, controlling for fatigue measured just prior to beginning CT (baseline), in 3 groups of women: BC patients receiving Anth CT (N = 103 at baseline), BC patients receiving NoAnth CT (N = 155), and women without cancer (N = 145). Fatigue was measured by the Functional Assessment of Chronic Illness Therapy Fatigue scale where lower scores indicate greater fatigue. Scores &lt; 30 indicate severe fatigue. We used ANOVA and ANCOVA models (PROC GLM; SAS v. 9.4) to generate unadjusted and adjusted mean fatigue scores in the 3 groups at the relevant time point. Given that selection to CT type was not random, we further adjusted for patient characteristics that influence treatment type (stage and comorbidities) in a model with the two CT groups only. Results: Mean age of participants (75.7% White and 18.1% Black) was 53.9 years. Among BC patients, the Anth group had higher tumor stage compared to the NoAnth group. Both cancer treatment groups reported significantly greater (unadjusted) fatigue pre-chemotherapy and at 3 months than healthy controls, but did not differ from each other. Adjusting for age and baseline fatigue, 3-month fatigue scores were significantly worse for the two CT groups (32.3 for Anth group, 34.3 for the NoAnth group) compared to the controls (44.6) (p &lt; .0001). In a model of cancer patients only, the difference between Anth and NoAnth groups remained non-significant (p = 0.10), after adjusting additionally for number of comorbidities and cancer stage. The unadjusted percentage of women with severe fatigue at 3 months was significantly greater for the BC patients (39% in the Anth group; 38% in the NoAnth group) compared to the healthy controls (1%), but again the two chemotherapy groups were not significantly different from each other. Adjustment for covariates listed above did not change this finding. Conclusions: Analyses support previous studies showing significant fatigue among BC patients treated with CT compared to women without cancer. Our data suggest that fatigue significantly impacts patients receiving CT irrespective of the regimen selected.[Table: see text]
Antimetastatic effect of benzimidazole derivative on the model of melanoma B16 in the experiment.
Authors: L. Z. Kurbanova, Nataliya Shevchenko, Ekaterina V. Verenikina, Ekaterina Fedorovna Komarova, Elena V. Filatova, Irina A. Khomutenko, Anna S. Goncharova, Ekaterina A. Lukbanova, D. V. Khodakova, A. V. Galina, Maria V. Mindar, Ekaterina V. Zaikina, Elizaveta Komarova
Journal: Journal of Clinical Oncology (2022)

e21562 Background: Study of the influence of a pharmacological substance dihydrobromide-2-(3,4-dihydroxyphenyl)-9-diethylaminoethylimidazo-[1,2-a] benzimidazole on the tumor growth on a model of experimental transplantable B16 melanoma in mice. Methods: B16 melanoma strain were transplanted subcutaneously to 80 female C57/Bl6 mice weighing 18-20 g. Intragastric dihydrobromide-2-(3,4-dihydroxyphenyl)-9-diethylaminoethylimidazo-[1,2-a] benzimidazole injections (0.5 ml a day) began 48 h after tumor transplantation once a day for 10 days at single doses of 50, 220 and 500 mg/kg (groups 1, 2 and 3, respectively). Mexidol was used for comparison, and saline as control (injected at similar regimens and doses). Results: Intragastric enoxifol injections did not significantly inhibit the melanoma growth. Only group 2 showed inhibition of the tumor growth by 48.7 % on day 22. Median survival of mice in all experiment groups was similar to that in the control group. The number of metastatic nodes in the lung tissues in groups 1, 2 and 3 decreased by 2.1, 4.8 and 2.5 times, respectively, compared to controls. The average index of metastasis inhibition was 71.3 % in all groups being 1.3 times higher than in the mexidol group (54.2 %). Conclusions: The revealed significant changes in parameters of the metastatic activity of the tumor suppose that dihydrobromide-2-(3,4-dihydroxyphenyl)-9-diethylaminoethylimidazo-[1,2-a] benzimidazole at all studied doses has a greater effect on the development of spontaneous lung metastases and metastasis rates than on the growth of primary B16 melanoma in mice.
A timely administration of metastasis-directed therapy can reduce the risk of disease progression in men with positive 68Ga-PSMA PET/CT for biochemical recurrence after radical prostatectomy
Authors: E. Mazzone, G. Gandaglia, A. Stabile, V. Chcchiara, E. Zaffuto, V. Mirone, F. Pellegrino, L. Nocera, F. Barletta, L. Toneatto, S. Scuderi, G.O. Cirulli, D. Robesti, R. Leni, A. Pellegrino, F. Montorsi, A. Briganti
Journal: European Urology (2022)
A real-world study update: Efficacy and safety of anlotinib for advanced non-small cell lung cancer.
Authors: Jinlin Wang, Tienan Yi, Youhong Dong, Xinhua Xu, Fengjun Cao, Ruizhi Ran, Yifa Yin, Yinping Li, Yang Fu, Yanhua Xu, Li Kuang, Guiming Chen, Guangqiao Qu, Jun Li, Zhiguo Luo, Yuan Chen, Qibin Song, Qian Chu
Journal: Journal of Clinical Oncology (2022)

e21106 Background: Anlotinib is an oral novel receptor tyrosine kinases (RTKs) inhibitor targeting multiple RTKs including VEGFR, PDGFR, FGFR, and c-kit. Due to its high efficacy and low side effects in ALTER 0303 trial, Anlotinib has been approved as a 3rd line therapy for pts with advanced non-small cell lung cancer (NSCLC) by NMPA in May 2018. The interim results of our real-world study suggested anlotinib substantially prolonged the progression-free survival (PFS) with manageable toxicity in later lines treatment of advanced NSCLC patients. Here, we update our latest results on the treatment experience in a broad NSCLC population. Methods: This is a multi-center, non-interventional, prospective real-world study. All registered data are collected from real-life clinical practice setting. Patients with advanced NSCLC treating with anlotinib were included. The primary endpoint was PFS, and the secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety. Results: As of January 2022, a total of 371 pts were enrolled, of whom 347 were evaluable, with a median age of 63 years, 232 males (66.9%). There were 40 pts (11.5%) with brain metastasis, 52 pts (15.0%) with bone metastasis, and 29 pts (8.4%) with liver metastasis at baseline. 109 pts (31.4%) received anlotinib as first/second line treatment, whereas 238 pts (68.6%) as third/later line treatment. In the overall population, DCR and ORR were 84.7% and 18.7% respectively. The mPFS was 6.3 months (95%CI, 5.7, 6.9) and the mOS was 12.2 months (95%CI, 9.5,14.9). Subgroup analysis showed more details. A trend towards better ORR (33.3%) was observed in the first line setting while a significantly better DCR (89.5%) was observed in the second line setting. The mPFS of first-/second-line treatment (6.9 months) was longer than that of the third-line or above treatment (5.8 months). The mOS of the first-/second- and third-line or above treatment were 10.4 (7.8,13) and 13.5 (8.9,18.1) months respectively. 52 pts (15%) had any grade of adverse events, of which 10 pts (2.9%) had grade 3 or above AEs. The most common AEs were hypoalbuminemia (3.5%), alanine aminotransferase reduction (1.4%), proteinuria (1.2%) and hyponatremia (1.2%). Conclusions: The updated results showed that anlotinib prolonged not only PFS but also OS significantly with a favorable safety profile, especially for OS benefits in third-line or later treatment. These data also indirectly revealed that anlotinib is a promising treatment option for patients with advanced NSCLC despite of treatment line in the real world.
Analysis of patients with relapsed small cell lung cancer (SCLC) receiving single-agent lurbinectedin in the phase 3 ATLANTIS trial.
Authors: Alejandro Navarro, Santiago Ponce Aix, Isidoro C. Barneto - Aranda, Egbert F. Smit, Jose Antonio Lopez-Vilariño, Antonio Nieto, Carmen Maria Kahatt, Ali Hassan Zeaiter, Sophie Cousin, Helge Bischoff, Jaromir Roubec, Konstantinos Syrigos, Luis Paz-Ares
Journal: Journal of Clinical Oncology (2022)

8524 Background: Lurbinectedin, a selective inhibitor of oncogenic transcription, received accelerated approval from the US FDA in June 2020 as monotherapy (3.2 mg/m 2 IV every 21 days) for adults with metastatic SCLC with disease progression on or after platinum-based chemotherapy. This approval was based on the overall response rate (35.2%) and duration of response (DOR; 5.3 months) observed in 105 patients from a phase 2 trial. The ATLANTIS trial (NCT02566993) investigated the combination of lurbinectedin 2.0 mg/m 2 IV + doxorubicin (DOX) 40.0 mg/m 2 IV versus topotecan or CAV. This post hoc analysis explored the efficacy and safety of single-agent lurbinectedin in patients who completed 10 cycles of the combination and then switched to lurbinectedin monotherapy per protocol. Methods: Eligible patients were ≥18 years of age with limited-stage or extensive-stage SCLC, 1 prior line of platinum-based chemotherapy (PD-1/PD-L1 inhibitors were also permitted), ECOG PS ≤2, and chemotherapy-free interval ≥30 days. Tumor assessments were per an independent review committee (IRC). Results: Patients who completed 10 cycles of lurbinectedin + DOX and switched to lurbinectedin monotherapy (n = 50) had a median age of 61.5 years (range: 43, 77); 62% were male; and 100% had an ECOG PS &lt; 2. The overall median number of cycles was 15 (range: 11, 47) and included a median of 5 (1, 37) cycles on monotherapy. The majority of patients who switched to lurbinectedin monotherapy maintained or improved their tumor response (Table). All 3 patients who achieved a complete response (CR) on combination therapy maintained their CR on monotherapy. Of the 26 patients with a partial response (PR) on combination therapy, 3 (12%) achieved a CR and 15 (58%) maintained their PR. Of the 19 patients with stable disease (SD) on combination therapy, 3 (16%) improved from SD to PR (n = 2) or CR (n = 1) and 8 (42%) maintained SD. The median DOR was 8.3 months (95% CI: 7.1, 11.0). The median overall survival (OS) was 20.7 months (95% CI: 15.7, 24.8). Grade 3/4 hematologic abnormalities based on laboratory assessment included lymphopenia (36%), anemia (16%), thrombocytopenia (12%), neutropenia (12%), and leukopenia (10%). Febrile neutropenia was reported in 4% of patients. Conclusions: Patients with relapsed SCLC in ATLANTIS who completed 10 cycles of lurbinectedin + DOX combination and switched to lurbinectedin monotherapy tended to maintain or improve their tumor response (including an increase in CRs), with favorable OS and DOR and acceptable tolerability with no new safety signals. Clinical trial information: NCT02566993. [Table: see text]
Tet2 deficiency drives liver microbiome dysbiosis triggering Tc1 cell autoimmune hepatitis
Authors: Surya P. Pandey, Mackenzie J. Bender, Alex C. McPherson, Catherine M. Phelps, Luzmariel Medina Sanchez, Mohit Rana, Lee Hedden, Kishan A. Sangani, Li Chen, Jake H. Shapira, Magdalena Siller, Chhavi Goel, Elena F. Verdú, Bana Jabri, Alexander Chang, Uma R. Chandran, Steven J. Mullett, Stacy G. Wendell, Aatur D. Singhi, Jeremy S. Tilstra, Joseph F. Pierre, Gavin E. Arteel, Reinhard Hinterleitner, Marlies Meisel
Journal: Cell Host & Microbe (2022)
Pemigatinib in Chinese patients with advanced/metastatic or surgically unresectable cholangiocarcinoma including FGFR2 fusion or rearrangement: Updated data from an open-label, single-arm, multicenter phase II study (CIBI375A201 study).
Authors: Guoming Shi, Xiaoyong Huang, Tianfu Wen, Tianqiang Song, Ming Kuang, Haibo Mou, Lequn Bao, Hai-Tao Zhao, Hong Zhao, Xielin Feng, Bixiang Zhang, Tao Peng, Yubao Zhang, Xiangcheng Li, Hongsheng Yu, Yu Cao, Yang Luo, Mingxia Chen, Jia Fan, Jian Zhou
Journal: Journal of Clinical Oncology (2022)

e16183 Background: Pemigatinib is a selective FGFR inhibitor that showed effectiveness and tolerability in patients with cholangiocarcinoma with FGFR2 fusion or rearrangement. However, pemigatinib has not been investigated in Chinese population with cholangiocarcinoma (CCA). Initial efficacy and safety data were previously presented (G-M. Shi et al. ESMO 2021; NCT04256980). Here, we report updated follow-up results from the phase II study. Methods: Patients aged 18 years or older with recurrent or metastatic CCA that failed at least one prior systemic therapy were enrolled. In Part 1, 3 subjects were enrolled regardless of the FGFR2 status and were treated at 9 mg pemigatinib. The other 31 subjects with documented FGFR2 fusion or rearrangement were enrolled in Part 2 and received 13.5 mg pemigatinib. From 2/26/2020 to 12/20/2021, all the subjects in both parts were orally given pemigatinib QD on a 2 weeks on/1 week off schedule until disease progression, unacceptable toxicity, withdrawal of consent, or physician decision. The primary efficacy end point was ORR assessed by independent radiological review committee (IRRC) per RECIST V1.1 in 31 patients enrolled in Part 2. Results: As of the data cutoff date (Dec 20 th , 2021), with a median follow up of 12.6 (11.8, 14.2) months, among 30 efficacy evaluable subjects with 1 participant excluded due to inadequate FGFR2 aberrant frequency, the updated confirmed objective response rate (ORR) was 60% (95% CI: 42.5%, 77.5%) per RECIST 1.1. The median DOR was 8.3 months (95% CI: 6.5, 11.2), and with 8 pts still maintaining tumor control of partial response. The updated median PFS was 9.1 months (95% CI: 7.8, 11.0). The DCR was also 100% (95% CI: 100%, 100%). All 34 subjects were included for safety analysis. As of data cutoff the safety profile was consistent with the primary analysis, with no new safety signals or concerns identified. With the longer follow up time, the frequency of grade 3 or higher TRAEs was increased to 26.5%. One patient experienced TRAE leading to treatment discontinuation, while no TRAE leading to death was observed or reported. TEAEs leading to dose interruption or dose reduction occurred in 23.5% and 14.7% of patients, respectively. Conclusions: Pemigatinib was high response rate and manageable tolerability in Chinese patients with recurrent or metastatic cholangiocarcinoma with FGFR2 fusion or rearrangement. Editorial acknowledgement: Guoming Shi and Xiaoyong Huang contributed equally to this work. Clinical trial information: NCT04256980.
Assessing the regional variability of a pre-biopsy mpMRI and targeted prostate cancer diagnostic pathway
Authors: D.T. Reddy, D. Eldred-Evans, M. Connor, F. Hosking-Jervis, M. Bertoncelli Tanaka, H. Bhola-Stewart, W. Maynard, C. Khoo, T. Shah, E. Bass, H.J. Lee, S. Ahmad, M. Noureldin, S. Joshi, E. Pegers, K. Wong, H. Tam, D. Hrouda, M. Winkler, S. Gordon, H. Qazi, H. Ahmed
Journal: European Urology (2022)
BTA stat®, Alere NMP22® BladderChek®, UBC® rapid test, and uromonitor® in comparison to cytology as tumor marker for urinary bladder cancer: New results of a german multicentre-study
Authors: T.H. Ecke, C. Meisl, S. Hofbauer, F. Labonté, T. Schlomm, F. Friedersdorff, A. Gössl, D. Barski, T. Otto, C. Grunewald, G. Niegisch, M. Hennig, M. Kramer, S. Koch, S. Hallmann
Journal: European Urology (2022)
Trends in ethnic-specific colorectal cancer mortality in patients with and without diabetes in the United States: A CDC database population-based study 2011-2019.
Authors: Abdul Rahman Al Armashi, Anas Al Zubaidi, Faris Hammad, Dina Elantably, Kanchi Patell, Francisco Somoza-Cano, Apoorva Krishna Chandar, Keyvan Ravakhah, Akram Alkrekshi
Journal: Journal of Clinical Oncology (2022)

3545 Background: Colorectal cancer (CRC) is the third most frequent type of cancer and the second most lethal in both sexes combined. CRC is strongly associated with both environmental and genetic risk factors. Previous studies reported an increased mortality in CRC patients with diabetes mellitus, however, the interplay between ethnicity and diabetes mellitus was not explored. This study analyzes trends in mortality across ethnic groups and assess the impact of diabetes mellitus. Methods: We queried the Multiple Cause of Death database (International Classification of Diseases, 10th revision) between 2011 and 2019, we identified all patients (Hispanic and non-Hispanic origin) who died of a malignant neoplasm of the colon, rectosigmoid junction, and rectum {Codes C18.x to C20.x reported as the underlying cause of death (UCD)}. Then we identified the same group (UCD) among individuals with diabetes (Insulin-dependent diabetes mellitus and non-insulin-dependent diabetes mellitus) (Codes E10.x to E11.x reported as multiple causes of death). Age-adjusted mortality rates per million persons (PMP) were estimated, standardized to US census data from 2000, and stratified by Hispanic origin. Results: In the general population, a total of 464,058 deaths from CRC were identified, with an overall age- adjusted mortality rate of 137.9 PMP (Hispanic: 109.3, Non-Hispanic: 141.1). Overall, age-adjusted mortality declined by 13% among Hispanic, from 118.1 PMP in 2011 to 102.9 PMP in 2019, and by 8% among non-Hispanic, from 153.3 PMP in 2011 to 141.1 PMP in 2019. In the diabetic population, a total of 8679 CRC death were identified, with an overall age-adjusted mortality rate of 2.6 PMP (Hispanic: 3.6, Non-Hispanic: 2.5). Age-adjusted mortality increased by 32% in Hispanic from 3.1 PMP in 2011 to 4.1 PMP in 2019 and by 13% in non-Hispanic from 2.4 PMP in 2011 to 2.7 PMP in 2019. Conclusions: This study concludes that between 2011 and 2019, the CRC mortality was reduced in both Hispanic and non-Hispanic in the general population. Notably, this tendency was not observed in the diabetic population, where mortality increased, particularly among Hispanic. Additional studies are warranted to determine the causes of the rise among diabetics and strategies for minimizing the disparity between Hispanic and non-Hispanic. [Table: see text]
Vitamin D insufficiency as a peripheral neuropathy risk factor in white and black patients in SWOG 0221.
Authors: Ciao-Sin Chelsea Chen, Gary Zirpoli, Susan McCann, William E. Barlow, George Thomas Budd, Lajos Pusztai, Gabriel N. Hortobagyi, Andrew K. Godwin, Alastair Mark Thompson, Christine B. Ambrosone, Kathleen A Stringer, Daniel Louis Hertz
Journal: Journal of Clinical Oncology (2022)

12023 Background: Peripheral neuropathy (PN) is a treatment-limiting toxicity of paclitaxel. Black patients have higher rates of PN and vitamin D insufficiency, and our prior work suggests vitamin D insufficiency increases risk of paclitaxel-induced PN. The objective of this study was to validate that patients with vitamin D insufficiency have higher risk of paclitaxel-induced PN and investigate whether this explains racial disparities in PN risk. Methods: This retrospective validation study was conducted in the phase III SWOG 0221 (NCT00070564) trial comparing paclitaxel-containing chemotherapy regimens for early-stage breast cancer. Pre-treatment 25-hydroxy-vitamin D was quantified in cryopreserved serum. Males and patients who received less than a third of the paclitaxel treatment were excluded. The association between vitamin D insufficiency (≤20 ng/mL) and grade 3+ sensory PN was tested via logistic regression and then adjusted for self-reported race, age, paclitaxel schedule (QW vs Q2W), and body mass index. Results: Of the 1,116 female patients in the analysis, 169 (15.1%) experienced PN and 376 (33.7%) had vitamin D insufficiency. Vitamin D insufficiency was associated with higher PN risk (19.4% vs 13.0%, OR = 1.62, p = 0.005, Data Table). The association was borderline significant (OR = 1.44, p = 0.056) after adjustment for black race (OR = 2.41, p = 0.001), paclitaxel schedule (OR = 2.22, p &lt; 0.001), and age (OR = 1.03, p = 0.005). Compared with white patients (n = 943), black patients (n = 99) had more prevalent vitamin D insufficiency (77.8% vs 28.6%, OR = 8.72, p &lt; 0.001) and increased PN risk (29.3% vs 13.5%, OR = 2.66, p &lt; 0.001); adjusting for vitamin D insufficiency decreased but did not eliminate the higher PN risk in black patients (OR = 2.23, p = 0.002). Conclusions: Vitamin D insufficiency increases risk of paclitaxel-induced PN and partially explains the higher risk of PN in black patients. Prospective trials are needed to test whether vitamin D supplementation lessens PN and reduces disparities in treatment outcomes. [Table: see text]